Drug information update : paliperidone palmitate for schizophrenia

Aims and method To review the evidence for the use of paliperidone palmitate for people with schizophrenia and schizophrenia-like illnesses. We searched the Cochrane Schizophrenia Group Specialised Register and contacted the manufacturer of paliperidone palmitate, the US Food and Drug Administration, and the authors of papers that reported study results. Results Based on the evidence from five short-term, placebo-controlled studies, paliperidone palmitate is efficacious as an antipsychotic. Its adverse effects are similar to those of the closely related compounds paliperidone and risperidone. Extrapyramidal side-effects, weight gain and tachycardia are more common with paliperidone palmitate than placebo. Paliperidone palmitate was associated with substantial increases in serum prolactin but not with increased sexual side-effects in these studies. In two studies paliperidone palmitate was similar to depot risperidone. Clinical implications Paliperidone palmitate is an effective antipsychotic whose optimal dose appears to be between 39 and 234 mg every 4 weeks. We have no data assessing its long-term effectiveness or comparing it with any long-acting injected antipsychotic other than depot risperidone.


Search methods
We searched the Cochrane Schizophrenia Group Specialised Register for randomised controlled trials (RCTs) comparing paliperidone palmitate with any other treatment for schizophrenia.We inspected references of identified studies The Psychiatrist (2013), 37, 164-166, doi: 10.1192/pb.bp.113.042739 1 Behavioral Health Service, Denver Health, Denver, Colorado, USA; 2 University of Colorado, Aurora, USA; 3 Columbia University, New York, USA Correspondence to Abraham M. Nussbaum (abraham.nussbaum@dhha.org)First received 11 Jan 2013, accepted 28 Jan 2013 Aims and method To review the evidence for the use of paliperidone palmitate for people with schizophrenia and schizophrenia-like illnesses.We searched the Cochrane Schizophrenia Group Specialised Register and contacted the manufacturer of paliperidone palmitate, the US Food and Drug Administration, and the authors of papers that reported study results.

Results
Based on the evidence from five short-term, placebo-controlled studies, paliperidone palmitate is efficacious as an antipsychotic.Its adverse effects are similar to those of the closely related compounds paliperidone and risperidone.Extrapyramidal side-effects, weight gain and tachycardia are more common with paliperidone palmitate than placebo.Paliperidone palmitate was associated with substantial increases in serum prolactin but not with increased sexual side-effects in these studies.In two studies paliperidone palmitate was similar to depot risperidone.
Clinical implications Paliperidone palmitate is an effective antipsychotic whose optimal dose appears to be between 39 and 234 mg every 4 weeks.We have no data assessing its long-term effectiveness or comparing it with any long-acting injected antipsychotic other than depot risperidone.for further trials and contacted the manufacturers of paliperidone palmitate, the US Food and Drug Administration and authors of relevant reports for additional material.We used RevMan version 5.1 software on Windows to conduct the analyses.All relevant RCTs were included.

Data collection and analysis
Data were analysed on an intention-to-treat basis.When appropriate, we calculated risk ratios (RR) and 95% confidence intervals with the number needed to benefit/ harm statistic (NNB/NNH).We calculated weighted mean differences (WMD) for continuous data.

Paliperidone palmitate v. depot risperidone
Two additional studies 14,15 compared paliperidone palmitate with depot risperidone (n = 1969).In these flexibly dosed trials, the mean doses of paliperidone palmitate were 73.3 mg and 104.6 mg every 4 weeks compared with depot risperidone at mean doses of 35.3 mg and 31.7 mg every 2 weeks.There was no difference for leaving these studies early for any reason between paliperidone palmitate and depot risperidone (n = 1969, 2 RCTs: RR = 1.12, 95% CI 1.00-1.25).Those receiving paliperidone palmitate were no more likely to have a recurrence of psychotic symptoms (n = 1961, 2 RCTs: RR = 1.23, 95% CI 0.98-1.53).There were a total of six deaths in these two trials, with five in the paliperidone palmitate groups.Although this difference was not significant (n = 1967, 2 RCTs: RR = 3.62, 95% CI 0.60-21.89),the small number of these events and wide confidence interval makes it unclear whether this finding is meaningful.Patients randomised to paliperidone palmitate were significantly less likely to use anticholinergic medications (n = 1587, 2 RCTs: RR = 0.67, 95% CI 0.55-0.82;NNB 13, 95% CI 10-24).
We found no data regarding service use, quality of life, patient satisfaction or cost.Similarly, we found no randomised studies that compared paliperidone palmitate with any other treatments for schizophrenia or schizophrenia-like illnesses.

Discussion
In short-term studies, paliperidone palmitate is an efficacious antipsychotic drug.Its adverse effects are similar to oral paliperidone, oral risperidone and depot risperidone.Extrapyramidal side-effects, weight gain and tachycardia are more common with paliperidone palmitate than placebo.Paliperidone palmitate is associated with substantial increases in serum prolactin.Used at mean doses of approximately 70-110 mg every 4 weeks, it appears comparable in efficacy and tolerability with depot risperidone used at mean doses of approximately 35 mg every 2 weeks. 8,16People who received paliperidone palmitate were significantly less likely to receive anticholinergic medications.Paliperidone palmitate has two practical advantages over depot risperidone in that it does not need to be refrigerated and can be administered monthly rather than bi-weekly, but we found no clear benefit of paliperidone palmitate over depot risperidone.
This study confirms our suspicion that paliperidone palmitate will affect people with schizophrenia similarly to depot risperidone.For individual clinicians to select paliperidone palmitate over other long-acting injectable antipsychotics on the basis of appropriate evidence, researchers will need to conduct longer-term pragmatic studies that more closely resemble the lived experience of patients with schizophrenia.Appropriate comparators include fluphenazine decanoate, haloperidol decanoate, depot olanzapine and depot risperidone.Clinicians would also benefit from studies that assess the efficacy, adverse effects and safety of long-term use of paliperidone palmitate, including behaviour, mortality, satisfaction with treatment and cost-effectiveness in comparison with oral antipsychotics.
Declaration of interest A.M.N. receives funding from the University of Chicago Program on Medicine and Religion for unrelated projects.T.S.S. receives funding from Agency for Healthcare Research and Quality and the National Institute of Mental Health for unrelated projects.